Summary
Our earlier work has demonstrated that EBV immortalized B lymphocytes are involved in a factor dependent autostimulatory cycle. Soluble growth stimulating activity was released into culture supernatants by these growing B cells. Growth enhancing (GE) media from B lymphocyte lines, immortalized by EBV infection, contained soluble factor(s) which modulated the Con A response of normal human mononuclear cells. Conditioned media from these lines affected the Con A response in a biphasic manner, stimulating the blastogenic response at lower concentrations, while inhibiting at higher concentrations. At stimulatory concentrations, the blastogenic response to Con A began earlier than in controls and was markedly enhanced by day 2. GE media reduced the initial response of purified B cells to pokeweed mitogen. GE media did not support growth of IL-2 dependent cells. GE media from some EBV-carrying B cell lines had measurable IL-1 activity in the mouse thymocyte PHA response. GE media from LPS stimulated B lymphocyte lines produced significant IL-1-like effects on stimulated mouse thymocytes. These results suggested that these B cell lines may produce IL-1-like factors that cooperate in T cell responses. The possibility that such factors may play a role in B lymphocyte transformation by EBV is discussed.
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Bach FH, Alter BJ, Widmer MB, Segal M, Dunlap B (1981) Cloned cytotoxic and non-cytotoxic lymphocytes in mouse and man: their reactivities and a large cell surface memebrane protein (LMP) differentiation marker system. Immunol Rev 54:5
Beneke J, Pearson GR (1980) Inhibitors of DNA synthesis produced by Herpesvirus transformed cell lines. J Immunol 124:2944
Blazar BA, Sutton LM, Strome M (1983) Self-stimulating growth factor production by B-cell lines derived from Burkitt's lymphomas and other lines transformed in vitro by Epstein-Barr Virus. Cancer Res 34:4562
Boyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation and of granulocytes by combining centrifugation and sedimentation. Scand J Clin Lab Invest (Suppl.) 21:77
DeLarco JE, Todaro GJ (1978) Growth factors from murine sarcoma virus transformed cells. Proc Natl Acad Sci 75:4001
Depper JM, Leonard WJ, Kronke M, Waldmann TA, Greene WC (1984) Augmented T cell growth factor receptor in HTLV-1 infected human Leukemic T cells. J Immunol 133:1691
DiPersio JF, Brennan JK, Litchman MA, Speiser BL (1978) Human cell lines that elaborate colony stimulating activity for the marrow cells of man and other species. Blood 51:507
Doolittle RF, Hunkapiller MW, Hood LE, DeWare SG, Robbins KC, Aaronson SA, Antoniades HN (1983) Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275
Downard J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, Ullrich A, Schlessinger J, Waterfield MD (1984) Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521
Epstein MA, Achong YM, Barr Y, Zajac, B, Henle G, Henle W (1966) Morphological and virological investigations on cultured Burkitt tumor lymphoblasts (strain Raji) J Natl Cancer Inst 37:347
Falkoff RJM, Muraguchi A, Hong JX, Butler JL, Dinarrello CA, Fauci AS (1983) The effects of interleukin 1 on human B cell activation and proliferation. J Immunol 131:801
Farrar JJ, Fieller-Farrar J, Simon PL, Hilfiker ML, Stadler BM, Farrar WL (1980) Thymoma production of T cell growth factor (Interleukin 2) J Immunol 125:2555
Ford RJ, Mihta SR, Franzini D, Montagna R, Lachman LB, Maizel AL (1981) Soluble factor activation of human B lymphocytes. Nature 294:261
Gerber P, Hoyer B (1971) Induction of cellular DNA synthesis in human leukocytes by Epstein Barr virus. Nature 231:46
Gordon J, Levy SC, Melamed MD, Aman P, Hughes-Jones, NC (1984) Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus. J Exp Med 159:1554
Gordon J, Levy SC, Melamed MD, English LS, Hughes-Jones NC (1984) Immortalized B lymphocytes produce B-cell growth factor. Nature 30:154
Griffin BE, Kavian L (1984) Immortalization of monkey epithelial cells by specific fragments of Epstein-Barr virus DNA Nature 399:78
Howard M, Mizel SB, Lachman L, Ansel J, Johnson B, Paul WE (1983) Role of interleukin 1 in anti-immunoglobulin induced B cell proliferation. J Exp Med 157:1529
Issekutz T, Chu E, Geha RS (1982) Antigen presentation by human B cells: T cells proliferation induced by Epstein Barr Virus B lymphoblastoid cells. J Immunol 129:1446
Klein E, Klein G, Nadkarni S, Wigzell H, Clifford P (1968) Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derivied cultures lines. Cancer Res 28:1300
Klein G, Giovanella B, Westman A, Stehlin J, Mumford D (1976) An EBV-genome negative cell line established from an American Burkitt lymphoma; receptor characteristics, EBV infectibility, and permanent conversion into EBV-positive sublines by in vitro infection. Intervirology 5:319
Leuthard P, Steck G, Burk R, Otto A (1980) Two different growth factors from an SV40 transformed BHK cell lines stimulate both migration and DNA synthesis. In: Jimenez de Asua, Levi-Montalcini, Shields Incobelli (eds.). Control mechanisms in animal cells, Raven Press New York pp 259
Lipsky PE, Thompson PA, Rosenwasser LJ, Dinarello CA (1983) The role of interleukin 1 in human B cell activation: inhibition of B cell proliferation and the generation of immunoglobulin-secreting cells by an antibody against human leukocytic pyrogen. J Immunol 130:2708
Rosen A, Gergely P, Jondal M, Klein G, Britton S (1977) Polyclonal Ig production after Epstein-Barr virus infection of human lymphocytes in vitro. Nature 267:52
Sanderson R, Vesole D, Jakway J, Talmage D (1980) A lymphocyte growth factor made by human lymphoid cell lines. Immunol Rev 51:177
Scala G, Kuang YD, Hall RE, Muchmore AV, Oppenheim JJ (1984) Accessory cell function of human B cells. 1. Production of both interleukin 1-like activity and an interleukin 1 inhibitory factor by an EBV-transformed human B cell line. J Exp Med 159:1637
Todaro GL, DeLarco JE, Marquardt H, Bryant M, Sherwin SA, Sliske AH (1979) Polypeptide growth factors produced by tumor cells and virus transformed cells: a possible growth advantage for the producer cells. Cold Spring Harbor Conference Cell Proliferation 6:113
Twardzik DR, Todaro GJ, Marquardt H, Reynolds FH, Stephenson JR (1982) Transformation induced by Abelson murine leukemia virus involves production of a polypeptide growth factor. Science 216:894
Waterford MD, Scrace GT, Whittle N, Stroobant P, Johnsson A, Wasteson A, Westermark B, Heldin CH, Huang JS, Deuel TF (1983) Platelet-derived growth factor is structurally related to the putative transforming protein p28SIS of simian sarcoma virus. Nature 304:38
Yoshida T, Kuratsiyi A, Takada A, Takada Y, Minowada J, Cohen S (1976) Lymphokine-like factors produced by human lymphoid cell lines with B or T cell surface markers. J Immunol 117:548
Zajac BA, Henle W, Henle G (1969) Autogenous and virus induced interferons from lines of lymphoblastoid cells. Cancer Res 29:1467
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Supported by grants from the Concern Foundation and the Brigham Surgical Foundation
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Blazar, B.A., Sutton, L.M. & Strome, M. Immunomodulating activity in supernatants from EBV immortalized lymphocytes. Cancer Immunol Immunother 22, 62–67 (1986). https://doi.org/10.1007/BF00205718
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DOI: https://doi.org/10.1007/BF00205718